EP0111209A2 - Sorbit, process for its preparation and its use - Google Patents

Abstract

The application relates to modified sorbitol with improved tableting properties, characterized by a melting point of approximately 96 ° C., a bulk density of 0.3 to 6 g / ml, a γ-sorbitol content of at least 90%, a purity of at least 98%, a specific surface area of 0.7 to 1.5 m² / g, a bending strength of more than 7 N / mm² at a pressing force above 10,000 N, a friability of less than 1% at a pressing force from 10,000 N, which is prepared by obtaining a sorbitol solution by hydrogenation of crystallized glucose at a temperature below 170 ° C, which is spray dried at a temperature of 140 to 170 ° C. The sorbitol obtained has a water content of less than 1%. Sorbitol is used for the production of pressed preparations.

Description

The invention relates to a modified sorbitol with improved tabletting properties.

Sorbitol is a widely used tablet base that is used, among other things, for chewable and lozenges. The particular advantage of sorbitol lies in the fact that it is in principle also suitable for direct pressing without any additional auxiliaries and additives. Sorbitol is generally obtained by hydrogenating starch hydrolyzates or by hydrogenating invert sugar with subsequent separation of mannitol. In solid form, it can be obtained both by crystallization and by spray drying.

Such sorbitol is generally not very suitable for producing satisfactory compressed products. Special processes have therefore been developed to produce a sorbitol suitable for better compression. For example, DE-A1 3009 875 describes a very special, complicated crystallization process by which a sorbitol suitable for pressing can be produced. Another special crystallization process is described in EP-Al 32288.

However, these processes require considerable technical effort, since the crystallization conditions must be adhered to very precisely in order to arrive at a usable product. In addition, the products pressed from the sorbitol types produced in this way are not yet completely satisfactory in terms of bending strength and abrasion resistance.

It was therefore the task of finding a sorbitol which can be produced more easily and which is improved in comparison with the known types of sorbitol, particularly in terms of its tableting properties, such as bending and abrasion resistance.

It has now been found that, surprisingly, sorbitol obtained by spray drying is also suitable for direct compression and in doing so even gives better results than the sorbitol obtained previously by crystallization. The prerequisite for this is that this sorbitol meets certain specifications or that certain parameters are adhered to in the production process.

• a) einen Schmelzpunkt von 96 °C
• b) eine Schüttdichte (nach DIN 53 912) von 0,3 - 0,6 g/ml
• c) einen y-Sorbitgehalt von mindestens 90 %
• d) eine Reinheit von mindestens 98 %
• e) eine spezifische Oberfläche (nach BET) von 0,7 bis 1,_{5 m}2_/g
• f) eine Biegefestigkeit von mehr als 7 _N/mm² bei einer Preßkraft oberhalb 10000 N
• g) eine Friabilität von weniger als 1 % bei einer Preßkraft ab 10 000 N.

The invention therefore relates to a modified sorbitol with improved tableting properties, which is characterized by

• a) a melting point of 96 ° C.
• b) a bulk density (according to DIN 53 912) of 0.3-0.6 g / ml
• c) a y-sorbitol content of at least 90%
• d) a purity of at least 98%
• e) a specific surface area (according to BET) of 0.7 to _{1.5 m} 2 _/ g
• f) a bending strength of more than 7 _{N /} mm ² with a pressing force above 10,000 N
• g) a friability of less than 1% with a pressing force of 10,000 N.

The invention also relates to a process for the production of sorbitol with improved tabletting properties, a sorbitol solution being obtained by hydrogenation of glucose-containing solutions and being obtained therefrom by spray drying, which is characterized in that a solution of crystallized glucose at a temperature below 170.degree is hydrogenated and the sorbitol solution thus obtained is spray-dried at a temperature of 140 to 170 ° C so that the product obtained has a water content of less than 1%.

Finally, the invention also relates to the use of sorbitol for the production of pressed preparations.

It is known to use so-called instant sorbitol obtained by spray drying as an additive to solid, also compressed, preparations. However, the previously known instant sorbitol could not be used alone, but had to be mixed with crystallized sorbitol, e.g. B. be cut according to DE-A1 3009875 or EP-A1 32288. The sole use of previously known instant sorbitol soon led to sticking to the tablet press and thus to its blocking.

However, it has now been found that the production of instant sorbitol can be controlled in such a way that a very compressible product is obtained. An essential prerequisite for this is that the sorbitol is largely free of by-products such as those found in e.g. B. can be formed by the choice of the starting material for the hydrogenation or by the hydrogenation conditions themselves. Even small amounts of the isomeric sugar alcohols idit, galactite or talit prevent perfect pressing and should therefore preferably be contained in a maximum of about 0.1%.

An essential prerequisite for the production of the sorbitol according to the invention is the use of crystallized glucose as the starting material for the hydrogenation. It is equally important that the hydrogenation takes place under gentle conditions, i. H. at temperatures which are below approximately 170 ° C., preferably below approximately 160 ° C.

The hydrogenation can otherwise be carried out under the usual conditions.

50 to 70% glucose solutions in the presence of a hydrogenation catalyst, such as. B. a supported nickel catalyst, especially Raney nickel, hydrogenated at hydrogen pressures of about 150 to about 200 bar, especially about 150 to about 180 bar. The solution is then cooled and separated from the catalyst. If necessary, the catalyst can be reused after working up. The analysis of the solutions shows that considerable amounts of by-products are formed even at temperatures of 170 ° C. Although these by-products do not interfere with the usability of the sorbitol as a sugar substitute, it has surprisingly been found that these by-products greatly impair the compressibility of the sorbitol. At hydrogenation temperatures below about 170 ° C and in particular below about 160 ° C, however, the formation of by-products is so greatly reduced that the sorbitol from the sorbitol solutions thus obtained does not have to be crystallized by complicated and time-consuming processes, but can be obtained by spray drying.

The sorbitol solution obtained from the hydrogenation solution after separating the catalyst and desalting can be used directly for spray drying. The solids content is previously adjusted to about 65 to about 75% by weight. The spraying is carried out by atomization using a centrifugal atomizer in a dry, centrifugally blown air stream heated to a temperature of 140-170 ° C. The amount of the sorbitol solution supplied and the hot air blown in are adjusted so that the sorbitol is dried to a water content of about 0.3 to about 1% by weight. In any case, the water content should be below 1% by weight.

The Sorbitteilchen which are thereby obtained by dehydration of the Sorbitlösungströpfchen are heated during the spray drying to a temperature of about 50 to about 70 ⁰ C, while the blown-in air is cooled to about the same temperature. The sorbitol is collected in containers and, after cooling, is suitable for the production of compressed products. In contrast to the previously known sorbitol instant, the material obtained by the process according to the invention can surprisingly be pressed with the addition of small amounts of a conventional lubricant, such as magnesium stearate, without sticking to the tabletting dies.

The sorbitol according to the invention is a sorbitol which, according to the Debye-Scherrer diagram, essentially consists of y-sorbitol. In contrast to the y-sorbitol known from DE-Al 3009875 and EP-Al 32288, the sorbitol according to the invention has an irregular surface. In the melting behavior (differential scanning calorimetry), the sorbitol according to the invention shows a sharp peak at approximately 96 ° C. The bulk density (according to DIN 53 912) is about 0.3 to 0.6 g / ml, the tamped density (according to DIN 53 194) is about 0.4 to 0.7 g / ml. Because of the irregular surface, the sorbitol according to the invention has a relatively high specific surface area of approximately 0.7 to approximately 1.5 m ² / g. The particle size can be controlled within wide limits by the spray drying process, but is generally much lower than in the case of the known compressible sorbitol types.

The sorbitol characterized in this way has a number of advantageous tableting properties.

Surprisingly, it can be established that much harder tablets can be produced with the sorbitol according to the invention with the same pressing force than with the known compressible sorbitol types. Since the optimal strength of lozenges is determined by the sucking behavior, this means that optimally hard tablets can be manufactured with very low compression forces. The bending strength as a measure of the hardness in the sorbitol according to the invention for tablets with a diameter of 10 mm and 0.3 g weight already reaches a value of about 7 N / mm ² with a pressing force of about 10,000 N and continues to increase to a value of about 11 N / mm ² at a pressing force of above 20,000 N. A compressible sorbitol obtained by crystallization, on the other hand, has only a bending strength of about 2.5 N / mm ² at a pressing force of 10,000 N, which only increases to one by increasing the pressing force to 20,000 N. Value of about 5 N / mm ² can be increased. Tableting machines with which the sorbitol according to the invention is pressed can therefore work at relatively low pressing forces and are therefore subject to much less wear.

In addition to the flexural strength, the abrasion resistance is particularly important for the quality of the tablets. Tablets pressed with the sorbitol according to the invention already have an abrasion resistance of less than 1% at a pressing force of 10,000 N, which decreases to an extremely low value of about 0.2 to 0.3% even at a pressing force of 15000 N or more. Tablets made from the known compressible sorbitol, on the other hand, have an abrasion of more than 6% at a pressing force of 5000 N, which only decreases to a final value of about 1% above 15000 N.

As already mentioned above, the strength of the tablets pressed from the sorbitol according to the invention with the same pressing force is very much higher than that of the tablets pressed from the known sorbitol. Tablets of the same strength can therefore be produced with the sorbitol according to the invention with a lower compression force and accordingly have a significantly higher volume than the comparison tablets. Since the sucking time corresponds to the volume of the tablet with the same tablet strength, tablets can be produced with the sorbitol according to the invention which have a significantly lower weight with the same sucking duration. In this way, considerable material savings can be achieved.

Due to the irregular surface of the sorbitol according to the invention is able to also larger amounts of additives such. B. of cocoa powder, dyes or other additives. The absorption capacity is significantly higher than that of the known compressible sorbitol types. Even when heavily loaded with additives, homogeneous mixtures are obtained and the compressed materials produced from them have a uniform appearance.

Due to the special production method by spraying an aqueous solution, it is possible; water-soluble additives, such as. B. dyes, vitamins and the like, to distribute completely homogeneously in sorbitol or the compressed products produced therefrom.

In contrast to tablets which were obtained by admixing dye to crystallized sorbitol before tabletting and which have a mottled surface, tablets produced according to the invention have a completely uniformly colored surface.

As already mentioned, the sorbitol according to the invention can only be added with the addition of small amounts of a conventional lubricant, e.g. 0.3 to 2% magnesium stearate, can be pressed directly. It is only essential that the water content, which is about 0.3 to about 1% by weight due to the production process according to the invention, does not rise to values above about 1% due to storage for too long at high atmospheric humidity. Sorbitol types with a higher water content can still be pressed perfectly in rooms with relatively low air humidity, but tend to stick to the plungers when they are pressed in rooms with high air humidity.

This good compressibility is not affected if additives such as. B. colorants, flavors or pharmaceutical active ingredients can be mixed through the appearance, taste and spectrum of activity of the preparation can be influenced.

As already mentioned above, the degree of purity of the sorbitol according to the invention should be above about 98%, since it has been found that the tablet properties can be influenced very negatively by impurities.

On the other hand, however, it was found that certain admixtures can increase the tablet strength, which is already very good anyway. Surprisingly, admixing mannitol in an amount of about 10 to 15% by weight before or after spray drying gives a product which already has a flexural strength of above 15,000 N reached over 15 N / mm ² . A particularly advantageous aspect of the present invention is therefore also sorbitol preparations which contain up to 15% by weight of mannitol.

The sorbitol according to the invention can be used alone or with additives for all customary purposes, in particular for the manufacture of chewable and lozenges. Due to the improved tabletting properties, the invention achieves considerable progress in this area.

Manufacturing examples:

Example 1:

A solution of 750 g of crystallized dextrose in 500 ml of deionized water is mixed in a 2-1 high-pressure autoclave with 50 g of moist Raney nickel and hydrogenated at 130 ° C. and 150 bar until the hydrogen uptake has ended. After the suspension has cooled, the catalyst is filtered off and washed with water.

The solids content of the solution consists of 99.2% by weight of sorbitol. By-products are only found in insignificant traces. The approximately 60% by weight solution thus prepared is sprayed using a centrifugal atomizer and dried with an air stream of 150 ° C. A sorbitol consisting essentially of the y-form with 0.8% by weight of residual moisture, a melting point of 96 ° C., a bulk density of 0.4 g / ml and a specific surface area (according to BET) of _1.0 m is obtained ² / g, an average grain size (a 'value of the RRSB distribution) of 500 microns, with 90% of the particles in the range of 280 up to 620 µm. When pressing the sorbitol with the addition of 0.3% by weight of magnesium stearate to tablets of 300 mg in weight and 10 mm in diameter on an eccentric press, the following results are achieved:

The flexural strength is measured using a modified hardness tester from Erweka, Heusenstamm, according to the P.H. List: Pharmaceutical Forms, 3rd edition, p. 105, Wiss. Verlagsgesellschaft mbH, Stuttgart, 1982, determined method described, the span being 6.7 mm.

The friability is determined in a friabilator from Erweka, Heusenstamm, with a running time of 6 minutes.

Example 2:

It is hydrogenated according to Example 1, but at a temperature of 150 ° C. The solids content of the solution obtained consists of 98.7% by weight of sorbitol. By-products are also only available in insignificant quantities here. The product obtained by spray drying analogously to Example 1 can be pressed without problems, results being obtained analogously to those given in Example 1.

Example 3:

It is hydrogenated analogously to Example 1, but at a temperature of 170 ° C. The solids content of the solution obtained consists of only 95.9% by weight of sorbitol. The by-products contained make the product obtained after spray drying analogous to Example 1 unsuitable for direct pressing, although the material could easily be used as a sugar substitute.

Example 4:

A solution of 750 kg of crystallized dextrose in 500 l of water is mixed with 35 kg of Raney nickel and hydrogenated at 180 ° C. and a pressure of 150 bar. The cooled and filtered solution after the end of the hydrogen uptake has a solids content which consists of 94.1% by weight of sorbitol.

The numerous by-products make the product obtained by spray drying analogous to Example 1 unsuitable for direct pressing, although this product could also be used as a sugar substitute.

A sorbitol prepared according to Example 1 or Example 2 can be used in the following application examples.

Example 5: Oral care tablets

Die Bestandteile werden vermischt und bei einem Preßdruck von 6000 N zu Tabletten von 6 mm Durchmesser und 100 mg Gewicht verpreBt.

The ingredients are mixed and pressed at a pressure of 6000 N into tablets 6 mm in diameter and 100 mg in weight.

Example 6: Menthol tablets

Die Bestandteile werden vermischt und bei einem PreBdruck von 14000 N zu Tabletten von 9 mm Durchmesser und einem Gewicht von 250 mg verpreßt.

The constituents are mixed and pressed at a pre-pressure of 14,000 N into tablets of 9 mm in diameter and a weight of 250 mg.

Example 7: Tablets for caries prophylaxis

Die Bestandteile werden vermischt und bei einem Preßdruck von 8000 N zu Tabletten von 7 mm Durchmesser und 100 mg Gewicht verpreßt.

The ingredients are mixed and pressed at a pressure of 8000 N to tablets of 7 mm in diameter and 100 mg in weight.

Example 8: Sorbitol Lozenges

Die Bestandteile werden vermischt und bei einem Preßdruck von 30000 N zu Tabletten von 13 mm Durchmesser und 500 mg Gewicht verpreßt.

The ingredients are mixed and pressed at a pressure of 30,000 N to tablets of 13 mm in diameter and 500 mg in weight.

Example 9: Vitamin C tablets

Die Bestandteile werden vermischt und bei einem Preßdruck von 30000 N zu Tabletten von 13 mm Durchmesser und 500 mg Gewicht verpreßt.

The ingredients are mixed and pressed at a pressure of 30,000 N to tablets of 13 mm in diameter and 500 mg in weight.

Example 10: Coffee tablets

Die Bestandteile werden vermischt und mit einem Preßdruck von 30000 N zu Tabletten von 13 mm Durchmesser und einem Gewicht von 500 mg verpreßt.

The ingredients are mixed and compressed with a pressure of 30,000 N to tablets of 13 mm in diameter and a weight of 500 mg.

Example 11: Cocoa tablets

Die Bestandteile werden vermischt und mit einem Preßdruck von 30000 N zu Tabletten mit einem Durchmesser von 13 mm und einem Gewicht von 500 mg verpreßt.

The ingredients are mixed and pressed with a pressure of 30,000 N into tablets with a diameter of 13 mm and a weight of 500 mg.

In all the recipes given, sorbitol instant sweetened with 0.1% saccharin or 0.2 aspartame or colored sorbitol instant can also be used.

Claims (3)

1. Modified sorbitol with improved tabletting properties, characterized by a) a melting point of about 96 ° C, b) a bulk density (according to DIN 53912) of 0.3 to 0.6 g / ml, c) a γ-sorbitol content of at least 90%, d) a purity of at least 98%, e) a specific surface area (according to BET) of 0.7 to 1.5 m ² / g, f) a bending strength of more than 7 N / mm ² with a pressing force above 10,000 N, g) a friability of less than 1% with a pressing force of 10,000 N. 2. A process for the production of sorbitol with improved tabletting properties, a sorbitol solution being obtained by hydrogenation of glucose-containing solutions and sorbitol being obtained therefrom by spray drying, characterized in that a solution of crystallized glucose is hydrogenated at a temperature below 170 ° C. and the so obtained Sorbitol solution is spray dried at a temperature of 140 to 170 ° C so that the product obtained has a water content of less than 1%. 3. Use of the sorbitol according to claim 1 for the production of pressed preparations.